Effects of alpha 2-adrenoceptor blockade and thyrotropin-releasing hormone (TRH) on the cardiovascular system in the rabbit.

The effects of two different doses of thyrotropin-releasing hormone on regional blood flows were studied in urethane-anaesthetized rabbits pretreated with the alpha 2-adrenergic antagonists yohimbine and idazoxan. The effects of yohimbine were also studied using unanaesthetized rabbits. Blood flow measurements were performed using the tracer microsphere method. Thyrotropin-releasing hormone was injected i.v. at a dose of either 0.1 mg kg-1 or 2.0 mg kg-1. Yohimbine and idazoxan did not modify the effect of thyrotropin-releasing hormone on mean arterial blood pressure. In the anaesthetized animals, blockade of the alpha 2-adrenoceptors resulted in a vasoconstriction in several peripheral organs and the vasoconstriction increased after thyrotropin-releasing hormone administration. Pretreament with yohimbine reduced total cerebral blood flow moderately and in such animals thyrotropin-releasing hormone elicited only minor cerebral blood flow effects. Pretreatment with idazoxan did not reduce the total cerebral blood flow and in such animals it increased from 53 +/- 1 to 75 +/- 4 g min-1 100 g-1 (P less than 0.01) after the administration of the lower dose of thyrotropin-releasing hormone and from 64 +/- 5 to 112 +/- 17 g min-1 100 g-1 (P less than 0.01) after the higher dose. In the conscious animals, yohimbine caused an increase in mean arterial blood pressure and heart rate. Vascular resistance increased in several organs. The cerebral blood flow decreased in white matter (P less than 0.05) and the caudate nucleus (P less than 0.05). The results indicate that there is a yohimbine-sensitive mechanism involved in the cerebrovasodilating effect of thyrotropin-releasing hormone in anaesthetized rabbits.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibition of the arginine/nitric oxide pathway causes bladder hyperactivity in the rat

The effects of thyrotropin-releasing hormone (TRH) on regional blood flows were studied in urethane-anaesthetized rabbits. Experiments were performed both with and without adrenergic antagonist pretreatment. The tracer microsphere method was used to measure blood flow. TRH (0.1 mg kg^-1) caused an increase in mean arterial blood pressure (MAP) from 9.8 ± 1 to 11.8 ± 0.8; a higher dose (1 mg kg^-1) increased the blood pressure to 15.2±1 kPa (P < 0.001). Total cerebral blood flow (CBF_tot) increased to 137 ± 10% (P < 0.05) of control at the lower dose and to 214±16% (P < 0.001), at the higher dose. A reduction in blood flow at both doses of TRH in several peripheral organs indicates that the pressor effect was mainly due to an effect on the peripheral vascular resistance. In prazosin-pretreated animals in which the MAP was normalized by ligation of the thoracic aorta, TRH elicited an increase in the CBF_tot to 131 ± 12% (P < 0.05) of control. In the iris, TRH caused vasodilation in prazosin-pretreated animals. In experiments with combined α- and β-adrenergic blockade, a non-adrenergic vasoconstricting effect of TRH was seen in some peripheral organs. The results indicate that TRH activates the sympathetic nervous system thus causing an increased vascular resistance and MAP; these effects are mediated mainly by an α₁-adrenergic mechanism. In the spleen, the gastric mucosa and the adrenal glands, the vasoconstriction caused by TRH was partly non-adrenergic. The vasodilation seen in the small intestine and the anterior uvea after TRH treatment and adrenoceptor blockade may be explained by effects on the parasympathetic nervous system. The vasodilating effect of TRH in the brain does not seem to involve α- or β-adrenergic mechanisms.     

Middle cerebral artery blood velocity depends on cardiac output during exercise with a large muscle mass

We tested the hypothesis that pharmacological reduction of the increase in cardiac output during dynamic exercise with a large muscle mass would influence the cerebral blood velocity/perfusion. We studied the relationship between changes in cerebral blood velocity (transcranial Doppler), rectus femoris blood oxygenation (near-infrared spectroscopy) and systemic blood flow (cardiac output from model flow analysis of the arterial pressure wave) as induced by dynamic exercise of large (cycling) vs. small muscle groups (rhythmic handgrip) before and after cardioselective β₁ adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.). During rhythmic handgrip, the increments in systemic haemodynamic variables as in middle cerebral artery mean blood velocity were not influenced significantly by metoprolol. In contrast, during cycling (e.g. 113 W), metoprolol reduced the increase in cardiac output (222 ± 13 vs. 260 ± 16%), heart rate (114 ± 3 vs. 135 ± 7 beats min^?1) and mean arterial pressure (103 ± 3 vs.112 ± 4 mmHg), and the increase in cerebral artery mean blood velocity also became lower (from 59 ± 3 to 66 ± 3 vs. 60 ± 2 to 72 ± 3 cm s^?1; P < 0.05). Likewise, during cycling with metoprolol, oxyhaemoglobin in the rectus femoris muscle became reduced (compared to rest; ?4.8 ± 1.8 vs. 1.2 ± 1.7 μmol L^?1, P < 0.05). Neither during rhythmic handgrip nor during cycling was the arterial carbon dioxide tension affected significantly by metoprolol. The results suggest that as for the muscle blood flow, the cerebral circulation is also affected by a reduced cardiac output during exercise with a large muscle mass.     

Cerebrovascular responses to haemorrhagic hypotension in anaesthetized cats. Effects of α-adrenoceptor antagonists

Haemorrhagic hypotension induces the phenomenon of cerebrovascular autoregulation and, concomitantly, involves an activation of the sympathetic nervous system. As brain vessels in cats have an atypical adrenoceptor distribution we studied the effects of an a-adrenoceptor antagonist on the autoregulatory response to haemorrhage. Cortical blood flow was studied by the H₂ technique in chloralose-anaesthetized cats subjected to a period of graded haemorrhage over 3 h. Three groups of cats were studied: control, i.e. those receiving saline (n= 10); yohimbine-treated (200/μg^-kg^-1 h^-1, n= 7); and prazosin-treated (50μg-kg^-1 h^-1, n= 6). In the control group, cortical blood flow remained relatively constant when mean arterial pressure was decreased from 102±1 mmHg (mean ± SE) to approximately 50.1 mmHg; thereafter, blood flow decreased with decreasing perfusion pressure. In the arterial pressure range 64-55 mmHg, cortical blood flow was significantly higher in the yohimbine group (109±12 ml-100 g^-1 min^-1) compared to the control group (69 ±6 ml-100 g^-1 min^-1) and remained higher in the yohimbine-treated cats at more extreme levels of hypotension. Blood flow did not fall significantly in the yohimbine-treated cats until mean arterial pressures of 31 ± 1 mmHg were attained. In the prazosin-treated cats, flow began to decrease at arterial pressures even greater than those observed in the control group. Thus, there is a sympathetic vasoconstriction of brain arteries that is primarily mediated by α₂-adrenoceptors in the feline cerebrovascular bed.     

Cerebral oxygenation is reduced during hyperthermic exercise in humans

Aim: Cerebral mitochondrial oxygen tension (P_mitoO₂) is elevated during moderate exercise, while it is reduced when exercise becomes strenuous, reflecting an elevated cerebral metabolic rate for oxygen (CMRO₂) combined with hyperventilation-induced attenuation of cerebral blood flow (CBF). Heat stress challenges exercise capacity as expressed by increased rating of perceived exertion (RPE). Methods: This study evaluated the effect of heat stress during exercise on P_mitoO₂ calculated based on a Kety-Schmidt-determined CBF and the arterial-to-jugular venous oxygen differences in eight males [27 ± 6 years (mean ± SD) and maximal oxygen uptake (VO_2max) 63 ± 6 mL kg⁻¹ min⁻¹]. Results: The CBF, CMRO₂ and P_mitoO₂ remained stable during 1 h of moderate cycling (170 ± 11 W, ∼50% of VO_2max, RPE 9–12) in normothermia (core temperature of 37.8 ± 0.4 °C). In contrast, when hyperthermia was provoked by dressing the subjects in watertight clothing during exercise (core temperature 39.5 ± 0.2 °C), P_mitoO₂ declined by 4.8 ± 3.8 mmHg (P < 0.05 compared to normothermia) because CMRO₂ increased by 8 ± 7% at the same time as CBF was reduced by 15 ± 13% (P < 0.05). During exercise with heat stress, RPE increased to 19 (19–20; P < 0.05); the RPE correlated inversely with P_mitoO₂ (r² = 0.42, P < 0.05). Conclusion: These data indicate that strenuous exercise in the heat lowers cerebral P_mitoO₂, and that exercise capacity in this condition may be dependent on maintained cerebral oxygenation.     

Enhanced cerebral CO2 reactivity during strenuous exercise in man

Light and moderate exercise elevates the regional cerebral blood flow by ~20% as determined by ultrasound Doppler sonography (middle cerebral artery mean flow velocity; MCA V _mean). However, strenuous exercise, especially in the heat, appears to reduce MCA V _mean more than can be accounted for by the reduction in the arterial CO₂ tension (P _aCO₂). This study evaluated whether the apparently large reduction in MCA V _mean at the end of exhaustive exercise relates to an enhanced cerebrovascular CO₂ reactivity. The CO₂ reactivity was evaluated in six young healthy male subjects by the administration of CO₂ as well as by voluntary hypo- and hyperventilation at rest and during exercise with and without hyperthermia. At rest, P _aCO₂ was 5.1±0.2 kPa (mean ± SEM) and MCA V _mean 50.7±3.8 cm s⁻¹ and the relationship between MCA V _mean and P _aCO₂ was linear (double-log slope 1.1±0.1). However, the relationship became curvilinear during exercise (slope 1.8±0.1; P<0.01 vs. rest) and during exercise with hyperthermia (slope 2.3±0.3; P<0.05 vs. control exercise). Accordingly, the cerebral CO₂ reactivity increased from 30.5±2.7% kPa⁻¹ at rest to 61.4±10.1% kPa⁻¹ during exercise with hyperthermia (P<0.05). At exhaustion P _aCO₂ decreased 1.1±0.2 kPa during exercise with hyperthermia, which, with the determined cerebral CO₂ reactivity, accounted for the 28±10% decrease in MCA V _mean. The results suggest that during exercise changes in cerebral blood flow are dominated by the arterial carbon dioxide tension.     

Middle cerebral artery blood velocity and plasma catecholamines during exercise

During dynamic exercise, mean blood velocity (V_mean) in the middle cerebral artery (MCA) demonstrates a graded increase to work rate and reflects regional cerebral blood flow. At a high work rate, however, vasoactive levels of plasma catecholamines could mediate vasoconstriction of the MCA and thereby elevate V_mean at a given volume flow. To evaluate transcranial Doppler-determined V_mean at high plasma catecholamine levels, seven elite cyclists performed a maximal performance test on a bicycle ergometer. Results were compared with those elicited during five incremental exercise bouts and during rhythmic handgrip when plasma catecholamines are low. During rhythmic handgrip the V_mean was elevated by 21±3% (mean±SE), which was not statistically different from that established during moderate cycling. However, at the highest submaximal and maximal work intensities on the bicycle ergometer, V_mean increased by 31±3% and 48±4%, respectively, and this was significantly higher compared to handgrip (P<0.05). During maximal cycling, plasma adrenaline increased from 0.21±0.04 nmol L^-1 at rest to 4.18±1.46 nmol L^-1, and noradrenaline increased from 0.79±0.08 to 12.70±1.79 nmol L^-1. These levels were 12- to 16-fold higher than those during rhythmic handgrip (adrenaline: 0.34±0.03 nmol L^-1; noradrenaline: 0.78±0.05 nmol L^-1). The increase in V_mean during intense ergometer cycling conforms to some middle cerebral artery constriction elicited by plasma catecholamines. Such an influence is unlikely during rhythmic handgrip compared with low intensity cycling.     

Middle cerebral artery blood velocity,arterial diameter and muscle sympathetic nerve activity during post-exercise muscle ischaemia

During exercise the transcranial Doppler determined mean blood velocity (V_mean) increases in the middle cerebral artery (MCA) and reflects cerebral blood flow when the diameter at the site of investigation remains constant. Sympathetic activation could induce MCA vasoconstriction and in turn elevate V_mean at an unchanged cerebral blood flow. In 12 volunteers we evaluated whether V_mean relates to muscle sympathetic nerve activity (MSNA) in the peroneal nerve during rhythmic handgrip and post-exercise muscle ischaemia (PEMI). The luminal diameter of the dorsalis pedis artery (AD) was taken to reflect the MSNA influence on a peripheral artery. Rhythmic handgrip increased heart rate (HR) from 74 ± 20 to 92 ± 21 beats min^?1 and mean arterial pressure (MAP) from 87 ± 7 to 105 ± 9 mmHg (mean ± SD; P < 0.05). During PEMI, HR returned to pre-exercise levels while MAP remained elevated (101 ± 9 mmHg). During handgrip contralateral MCA V_mean increased from 65 ± 10 to 75 ± 13 cm s^?1 and this was more than on the ipsilateral side (from 63 ± 10 to 68 ± 10 cm s^?1; P < 0.05). On both sides of the brain V_mean returned to baseline during PEMI. MSNA did not increase significantly during handgrip (from 56 ± 24 to 116 ± 39 units) but the elevation became statistically significant during PEMI (135 ± 86 units, P < 0.05), while AD did not change. Taken together, during exercise and PEMI, V_mean changed independent of an elevation of MSNA by more than 140% and the dorsalis pedis artery diameter was stable. The results provide no evidence for a vasoconstrictive influence of sympathetic nerve activity on medium size arteries of the limbs and the brain during rhythmic handgrip and post-exercise muscle ischaemia.     

Long-lasting coronary vasoconstrictor effects and myocardial uptake of endothelin-1 in humans

The effect of intravenous administration of the endothelium-derived vasoconstrictor peptide endothelin-1 (ET-1 0.2, 1 and 8 pmol kg^?1 min^?1) on coronary blood flow in relation to plasma ET-1 as well as blood lactate and glucose levels were investigated in six healthy volunteers. Coronary sinus blood flow was measured by thermodilution. Administration of ET-1 elevated arterial plasma ET 35-fold, dose-dependently increased mean arterial blood pressure from 95±5 mmHg to 110±6 mmHg (P<0.01) and reduced heart rate from 64±4 beats min^?1 to 58±4 beats min^?1 (P<0.05) at 8 pmol kg^?1 min^?1. Coronary sinus blood flow was reduced maximally by 23±4% (P<0.01) and coronary vascular resistance increased by 48±11% (P<0.01). Coronary sinus oxygen saturation decreased from 35±1% to 22±2% at 2 min after the infusion (P<0.01). A coronary constrictor response was observed at a 4-fold elevation in plasma ET. The reduction in coronary sinus blood flow lasted 20 min and coronary sinus oxygen saturation was still reduced 60 min after the infusion. Myocardial oxygen uptake or arterial oxygen saturation were not affected by ET-1. Myocardial lactate net uptake decreased by 40% whereas glucose uptake was unaffected. At the highest infusion rate there was a net removal of plasma ET by 24±3% over the myocardium (P<0.05). The results show that ET-1 induces long-lasting reduction in coronary sinus blood flow via a direct coronary vasoconstrictor effect in healthy humans observable at a 4-fold elevation in plasma ET-1. Furthermore, there is a net removal of circulating ET-1 by the myocardium.     

Role of adenosine in exercise‐induced human skeletal muscle vasodilatation

The role of adenosine in exercise‐induced human skeletal muscle vasodilatation remains unknown. We therefore evaluated the effect of theophylline‐induced adenosine receptor blockade in six subjects and the vasodilator potency of adenosine infused in the femoral artery of seven subjects. During one‐legged, knee‐extensor exercise at ～48% of peak power output, intravenous (i.v.) theophylline decreased (P < 0.003) femoral artery blood flow (F_aBF) by ～20%, i.e. from 3.6 ± 0.5 to 2.9 ± 0.5 L min^?1, and leg vascular conductance (VC) from 33.4 ± 9.1 to 27.7 ± 8.5 mL min^?1 mmHg^?1, whereas heart rate (HR), mean arterial pressure (MAP), leg oxygen uptake and lactate release remained unaltered (P = n.s.). Bolus injections of adenosine (2.5 mg) at rest rapidly increased (P < 0.05) F_aBF from 0.3 ± 0.03 L min^?1 to a 15‐fold peak elevation (P < 0.05) at 4.1 ± 0.5 L min^?1. Continuous infusion of adenosine at rest and during one‐legged exercise at ～62% of peak power output increased (P < 0.05) F_aBF dose‐dependently to level off (P = ns) at 8.3 ± 1.0 and 8.2 ± 1.4 L min^?1, respectively. One‐legged exercise alone increased (P < 0.05) F_aBF to 4.7 ± 1.7 L min^?1. Leg oxygen uptake was unaltered (P = n.s.) with adenosine infusion during both rest and exercise. The present findings demonstrate that endogenous adenosine controls at least ～20% of the hyperaemic response to submaximal exercise in skeletal muscle of humans. The results also clearly show that arterial infusion of exogenous adenosine has the potential to evoke a vasodilator response that mimics the increase in blood flow observed in response to exercise.     

Heart and brain circulation and CO2 in healthy men

Aim: To compare blood flow response to arterial carbon dioxide tension change in the heart and brain of normal elderly men. Methods: Thirteen healthy elderly male volunteers were studied. Hypercapnea was induced by carbon dioxide inhalation and hypocapnea was induced by hyperventilation. Myocardial blood flow [mL min^?1 × (100 g of perfusable tissue)^?1] and cerebral blood flow [mL min^?1 × (100 g of perfusable tissue)^?1] were measured simultaneously at rest, under carbon dioxide gas inhalation and hyperventilation using the combination of two positron emission tomography scanners. Results: Arterial carbon dioxide tension increased significantly during carbon dioxide inhalation (43.1 ± 2.7 mmHg, P < 0.05) and decreased significantly during hyperventilation (29.2 ± 3.4 mmHg, P < 0.01) from baseline (40.2 ± 2.4 mmHg). Myocardial blood flow increased significantly during hypercapnea (88.7 ± 22.4, P < 0.01) from baseline (78.2 ± 12.6), as did the cerebral blood flow (baseline: 39.8 ± 5.3 vs. hypercapnea: 48.4 ± 10.4, P < 0.05). During hypocapnea cerebral blood flow decreased significantly (27.0 ± 6.3, P < 0.01) from baseline as did the myocardial blood flow (55.1 ± 14.6, P < 0.01). However, normalized myocardial blood flow by cardiac workload [100 mL mmHg^?1 × (heart beat)^?1 × (gram of perfusable tissue)^?1] was not changed from baseline (93.4 ± 16.6) during hypercapnea (90.5 ± 14.3) but decreased significantly from baseline during hypocapnea (64.5 ± 18.3, P < 0.01). Conclusion: In normal elderly men, hypocapnea produces similar vasoconstriction both in the heart and brain. Mild hypercapnea increased cerebral blood flow but did not have an additional effect to dilate coronary arteries beyond the expected range in response to an increase in cardiac workload.     

Vascular effects of endothelin-1 in the cat; modification by indomethacin and l-NAME

Intravenous infusion of endothelin-1 (ET-1) in the cat, 60 pmol × kg body wt^-1x min^-1for 5 min, induced an increase in mean arterial blood pressure (MAP) of 41.3 ± 4.8 mmHg (n= 6; P < 0.001). Blood flow, as determined with radioactive microspheres, was reduced in many tissues. Reductions by 70–80% were observed in the choroid plexus, pineal and pituitary glands. Total cerebral blood flow was reduced by 18–23%. Pre-treatment with indomethacin or a combination of indomethacin and l -NAME caused vasoconstriction in many tissues and modified the responses to ET-1 in a variable way, suggesting that normally, ET-1 tends to release arachidonic acid metabolites and nitric oxide with great variations between different tissues. Intracerebroventricular infusion (i.c.v.) of ET-1, 10 pmol × kg body wt^-1x min^-1, caused an increase in MAP of 79 ± 11 mmHg (n= 6; P < 0.001). Regional blood flow in the medulla oblongata, medulla spinalis, choroid plexus, pineal and pituitary glands was reduced by 60–80%. Heart rate, cardiac output and coronary blood flow were significantly increased after 30 min i.c.v. infusion, indicating an activation of the heart, most probably as part of a central ischaemic response. Our results indicate that in many tissues the vasoconstrictive effect of ET-1 is influenced by indomethacin- and l -NAME-sensitive vasodilator mechanisms that are activated by the peptide. In the CNS, there may be marked effects on regional blood flow after i.c.v. infusion.     

The ethanol technique of monitoring local blood flow changes in rat skeletal muscle: implications for microdialysis

We have investigated the feasibility of monitoring local skeletal muscle blood flow in the rat by including ethanol in the perfusion medium passing through a microdialysis probe placed in muscle tissue. Ethanol at 5, 55, or 1100 mm did not directly influence local muscle metabolism, as measured by dialysate glucose, lactate, and glycerol concentrations. The clearance of ethanol from the perfusion medium can be described by the outflow/inflow ratio ([ethanol]_{collected dialysate}/[ethanol] _{Infused perfusion medium}), which was found to be similar (between 0.36 and 0.38) at all ethanol perfusion concentrations studied. With probes inserted in a flow-chamber, this ratio changed in a flow-dependent way in the external flow range of 5–20 μl min^-1. The ethanol outflow/inflow ratio in vivo was significantly (P < 0.001) increased (to a maximum of 127±2.8% and 144±7.4% of the baseline, mean ±SEM) when blood flow was reduced by either leg constriction or local vasopressin administration, and significantly (P < 0.001) reduced (to 62±6.4% and 43±4.4% of baseline) with increases in blood flow during external heating or local 2-chloroadenosine administration, respectively. Dialysate glucose concentrations correlated negatively with the ethanol outflow/inflow ratio (P < 0.01) and consequently decreased (to 46 ± 7.6% and 56 ± 5.6% of baseline) with constriction and vasopressin administration and increased (to 169 ± 32.5 % and 262 ± 16.7% of baseline) following heating and 2-chloroadenosine administration. Dialysate lactate concentrations were significantly increased (approximately 2-fold, P < 0.001) during all perturbations of blood flow. In conclusion, this technique makes it possible to monitor changes in skeletal muscle blood flow; however, methods of quantification remain to be established. The fact that blood flow changes were found to significantly affect interstitial glucose and lactate concentrations as revealed by microdialysis indicates that this information is critical in microdialysis experiments.     

Activation of sympathetic nerves exerts an inhibitory influence on afferent nerve-induced vasodilation unrelated to vasoconstriction in rat dental pulp

In order to elucidate a possible influence of the sympathetic nervous system on afferent nerve function, rat mandibular incisors were electrically stimulated and blood flow changes monitored in the incisor pulp of untreated and sympathectomized animals by a laser Doppler flowmeter. Monopolar electrical stimulation of the tooth (200 μA, 5 ms, 40 Hz, 1 s) in normal animals resulted in a transient reduction in pulpal blood flow (PBF) (16%, reduction, n= 10) followed by a small but long-lasting increase (11% increase). After administration of phenoxybenzamine or phentolamine (3 mg kg^-1, i.v.) the initial dip in PRF was reduced by 59% (P < 0.001) while the subsequent increase was enhanced by 185% (P < 0.001). Similarly, infusion of prazosin (50μg kg^-1, i.v.) and idazoxan (0.5 mg kg^-1 i.v.) significantly enhanced the increase in PBF by 118 and by 79%, respectively. In chronically sympathectomized animals the increase in PBF was 250% larger than that seen in untreated animals (P < 0.001). This increase in PBF was not further enhanced after α-adrenergic blockade. Acute resection of the superior cervical sympathetic ganglion, also resulted in some enhancement (by 56%) of the stimulation-induced increase in PBF (P < 0.01, n = 6). The increase in PBF was unaffected by infusion of timolol (150 μg kg^-1) and atropine (1 mg kg^-1) but was totally abolished by intravenous pre-treatment with capsaicin (1–3 mg kg^-1). The present results suggest that activation of sympathetic nerves exerts inhibitory effects on the afferent nerve-induced vasodilation in the rat incisor pulp unrelated to sympathetic vasoconstriction.     

Cerebral cortical blood flow in rabbits during parabolic flights (hypergravity and microgravity)

We studied the effect of gravity on cerebral cortical blood flow (CBF), mean arterial blood pressure () and heart rate in six rabbits exposed to parabolic flights. The CBF was obtained using a laser-Doppler probe fixed on to a cranial window. Before weightlessness, the animals were exposed to chest-to-back directed acceleration (1.8–2.0 g). The CBF values were expressed as a percentage of CBF_o (mean CBF during 60 s before the 1st parabola). Propranolol (1 mg · kg⁻¹ IV) was given after the 11th parabola and pentobarbital (12–15 mg · kg⁻¹ IV) after the 16th parabola. Before the administration of the drugs, CBF increased (P < 0.01) during hypergravity [i.e. maximal CBF 151 (SD 64)% CBF_o. Simultaneously increased [maximal , 119 (SD 11) mmHg (P < 0.01)]. At the onset of weightlessness, CBF and reached maximal values [194 (SD 96)% CBF_o (P < 0.01) and 127 (SD 19) mmHg, (P < 0.01) respectively]. The microgravity-induced increase in CBF was transient since CBF returned to its baseline value after 8 (SD 2) s of microgravity. After propranolol administration, CBF was not statistically different during hypergravity but an elevation of CBF was still observed in weightlessness. The increases in CBF and also persisted during weightlessness after pentobarbital administration. These data would indicate that CBF of nonanesthetized rabbits increases during the first seconds of weightlessness and demonstrate the involvement of rapid active regulatory mechanisms since CBF returned to control values within 8 (SD 2) s. We concluded that this elevation in blood flow was not related to stress because it persisted after the administration of propranolol and pentobarbital. Accepted: 6 November 1997     

Middle cerebral artery blood velocity during exercise with β‐1 adrenergic and unilateral stellate ganglion blockade in humans

A reduced ability to increase cardiac output (CO) during exercise limits blood flow by vasoconstriction even in active skeletal muscle. Such a flow limitation may also take place in the brain as an increase in the transcranial Doppler determined middle cerebral artery blood velocity (MCA V_mean) is attenuated during cycling with β‐1 adrenergic blockade and in patients with heart insufficiency. We studied whether sympathetic blockade at the level of the neck (0.1% lidocain; 8 mL; n=8) affects the attenuated exercise – MCA V_mean following cardio‐selective β‐1 adrenergic blockade (0.15 mg kg^?1 metoprolol i.v.) during cycling. Cardiac output determined by indocyanine green dye dilution, heart rate (HR), mean arterial pressure (MAP) and MCA V_mean were obtained during moderate intensity cycling before and after pharmacological intervention. During control cycling the right and left MCA V_mean increased to the same extent (11.4 ± 1.9 vs. 11.1 ± 1.9 cm s^?1). With the pharmacological intervention the exercise CO (10 ± 1 vs. 12 ± 1 L min^?1; n=5), HR (115 ± 4 vs. 134 ± 4 beats min^?1) and ΔMCA V_mean (8.7 ± 2.2 vs. 11.4 ± 1.9 cm s^?1) were reduced, and MAP was increased (100 ± 5 vs. 86 ± 2 mmHg; P < 0.05). However, sympathetic blockade at the level of the neck eliminated the β‐1 blockade induced attenuation in ΔMCA V_mean (10.2 ± 2.5 cm s^?1). These results indicate that a reduced ability to increase CO during exercise limits blood flow to a vital organ like the brain and that this flow limitation is likely to be by way of the sympathetic nervous system.     

Quantitative agreement between [15O]H2O PET and model free QUASAR MRI‐derived cerebral blood flow and arterial blood volume

The purpose of this study was to assess whether there was an agreement between quantitative cerebral blood flow (CBF) and arterial cerebral blood volume (CBVA) measurements by [¹⁵O]H₂O positron emission tomography (PET) and model‐free QUASAR MRI. Twelve healthy subjects were scanned within a week in separate MRI and PET imaging sessions, after which quantitative and qualitative agreement between both modalities was assessed for gray matter, white matter and whole brain region of interests (ROI). The correlation between CBF measurements obtained with both modalities was moderate to high (r²: 0.28–0.60, P < 0.05), although QUASAR significantly underestimated CBF by 30% (P < 0.001). CBV_A was moderately correlated (r²: 0.28–0.43, P < 0.05), with QUASAR yielding values that were only 27% of the [¹⁵O]H₂O‐derived values (P < 0.001). Group‐wise voxel statistics identified minor areas with significant contrast differences between [¹⁵O]H₂O PET and QUASAR MRI, indicating similar qualitative CBV_A and CBF information by both modalities. In conclusion, the results of this study demonstrate that QUASAR MRI and [¹⁵O]H₂O PET provide similar CBF and CBV_A information, but with systematic quantitative discrepancies. Copyright © 2016 John Wiley & Sons, Ltd.     

Effects of indomethacin on regional blood flow in conscious rabbits—a microsphere study

In an attempt to reveal the importance of prostaglandins in the control of regional blood flow 20 mg/kg b.wt. indomethacin was given i.v. in conscious resting rabbits. Regional blood flow determinations were made before and 20 min after the injection using the labelled microsphere technique. The blood flow in the stomach wall was reduced by 0.75 ± 0.17 g·min^-1·g^-1 from a level of 1.64 ± 0.24 g·min^-1·g^-1. In jejunum the corresponding figures were 0.44 ± 0.12 and 1.26 ± 0.17 and in the brain 0.29 ± 0.10 and 1.24 ± 0.10. The blood flow in the liver via the hepatic artery increased by 0.20 ± 0.02 g·min^-1·g^-1 from a level of 0.13 ± 0.02 g·min^-1·g^-1. In the retina there was a reduction in blood flow by 2.75 ± 1.03 mg·min^-1 from a starting level of 15.1 ± 2.3 mg·min^-1. In a number of other tissues investigated there were no significant effects of the drug. The results suggest that under resting conditions prostaglandins play a role in the control of blood flow in the gastrointestinal tract, the brain and the retina—tissues which are likely to be rather active under such conditions.     

Minimal effects of nitric oxide on spatial blood flow heterogeneity of the dog heart

 Eleven Beagle dogs were studied to elucidate the possible role of L-arginine-derived nitric oxide on local blood flow distribution in left and right ventricular myocardium. Local blood flow was determined in 256 samples from the left and 64 samples from the right ventricle per heart using the tracer microsphere technique (mean sample mass 319 ± 131 mg). Nitric oxide production was effectively inhibited by intravenous infusion of 20 mg/kg nitro-L-arginine methylester (L-NAME) as evidenced by a shift of the dose/response curve for the effect of intracoronary administration of bradykinin (0.004–4.0 nmol/min) on coronary blood flow. L-NAME enhanced left and right ventricular systolic pressures from 132 ± 18 to 155 ± 15 mm Hg and from 26 ± 3 to 29 ± 3 mm Hg respectively (both P = 0.043). Mean left ventricular blood flow was 1.14 ± 0.38 before and 0.99 ± 0.28 ml min^–1 g^–1 after L-NAME (P = 0.068), while right ventricular blood flow fell from 0.72 ± 0.28 to 0.53 ± 0.20 ml min^–1 g^–1 (P = 0.043). Coronary conductance of left and right ventricular myocardium fell by 31 and 43% respectively (both P = 0.043). The coefficient of variation of left ventricular blood flow was 0.26 ± 0.07 before and 0.29 ± 0.07 after L-NAME (P = 0.068), that of right ventricular blood flow was 0.27 before and after L-NAME. Skewness (0.51) and kurtosis (4.23) of left ventricular blood flow distribution were unchanged after L-NAME, while in the right ventricle skewness decreased from 0.54 to 0.09 (P = 0.043) and kurtosis (3.68) tended to decrease after L-NAME (P = 0.080). The fractal dimension (D = 1.20–1.27) and the corresponding nearest-neighbor correlation coefficient (r _n = 0.37–0.53) of left and right ventricular myocardium remained unchanged after infusion of L-NAME. From these results it is concluded that firstly, local nitric oxide release does not explain the higher perfusion of physiological high flow samples and secondly, that spatial myocardial blood flow coordination is not dependent on nitric oxide. Received: 11 July 1996 / Received after revision: 29 October 1996 / Accepted: 17 December 1996     

Vasoconstriction in active calf persists after discontinuation of combined exercise with high-intensity elbow flexion

The present study aimed to determine whether vasoconstriction in active calf occurring during combined exercise diminished or persisted when added low- and high-intensity elbow flexion exercise ceased and single leg exercise continued. Six active women (mean age, 21.2 years) participated in this study. During 10-min plantar flexion exercise at 10% of maximum voluntary contraction (MVC), elbow flexion exercise at 10% MVC was added over the 3rd and 4th min. Calf blood flow did not change significantly upon superimposition and cessation of this elbow flexion exercise. However, when elbow flexion exercise at 50% MVC was added during the 7th and 8th min, calf blood flow above the resting value (2.23±0.23 mL 100 mL^-1 min^-1) decreased significantly (P<0.05) from 6.72±0.87 (6th min) to 5.14±1.36 mL 100 mL^-1 min^-1 after 2 min of combined exercise and was accompanied by a similar change in the non-exercising calf blood flow value. The vascular conductance of the exercising calf decreased significantly (P<0.01) from 6.48±1.08 (6th min) to 3.11±1.27 mL 100 mL^-1 min^-1 mmHg^-1 at the end of the 2nd min of combined plantar flexion exercise with elbow flexion exercise at 50% MVC. After elbow flexion exercise at 50% MVC was discontinued and plantar flexion exercise at 10% MVC alone was performed, the vascular conductance in the exercising calf remained significantly low for the next 2 min. These results indicate that the vasoconstriction induced by adding high-intensity arm exercise is persistent, suggesting a major contribution of metabo-receptor-mediated vasoconstriction rather than central command- and mechano-receptor-mediated vasoconstriction.